delta 1, 4-pregnadiene-17alpha-ol-3-ones



Patented Dec. 25, 1951 lin, Mexico City, Mexico, assignors to *S'yn-texS. A., Mexico City, Mexico, a corporation of Mexico PATENT OFFICE NoDrawing. Application January 2a, 1950, Serial N0.1140,154

3 Claims.

The present invention relates to A -pregnadiene-17a-ol-3-ones. Moreparticularly the present invention relates to A -dien-3-ones of thel'la-hydroxy pregnane series. Compounds of this general character havesubstantial therapeutic value.

It has been found in accordance with the present invention that thesecompounds may be obtained by dibrominating the analogous ring Asaturated 3-ketoallosteroids to produce the 2,4-dibromo derivative andthereafter dehydrobrominating the 2,4-dibror'no derivative with asuitable base, such as collidine.

The present invention is directed in general to A -dien-3-ones of the1'7a-hYdlOXY pregnane series whether or not the cyclopentanophemanthrene ring is substituted in rings B, C or D, and whether or not thecompound is provided with a hydroxy group at the 21-position, or theaforementioned 21-hydroxy group has been esterified with a lower fattyacid, as for example acetic acid or propionic acid.

The present invention is especially directed to compounds which may becharacterized by the following general formula:

CHzR

CH3 L---OH wherein R. may be hydrogen or hydroxy or the correspondingesterified compounds with a lower fatty acid, as for example aceticacid, propionic acid, etc.

The following specific examples serve to illustrate the presentinvention but are not intended to limit the same.

Example I I To a solution of g. of allopregnane-l'laol-3,20-dione,prepared in accordance with the application of George Rosenkranz,Stephen Kaufmann, and John Pataki, Serial No. 116,624, filed September19, 1949, in 2 liters of glacial acetic at room temperature for at leastfive hours, di-

luted with water and filtered. The dried precipitate(2,4-dibromoallopregnane-17a-ol-3,20-dione) was purified byrecrystallization from ethyl acetate-hexane and was obtained ascolorless crystals, with a melting point of 183-185 C. withdecomposition), [aln 0 (chloroform. The dehydrobromination wasaccomplished by refluxing 1.82 g. of the above 2,4-dibromoallopregnane-17a-ol-3,20-dione for one hour with 9 cc. of collidine and partitioningthe resulting mixture between chloroform and dilute hydrochloric acid.After thorough washing of the organic layer and drying, the solvent wasevaporated and the residue was purified by direct recrystallization orchromatography over activated alumina; the resultant A-p-regnadien-17a-ol-3,20-di0ne possessed the following properties:melting point 232-234 C.[a]D +38.5 (chloroform), ultraviolet absorptionmaximum at 244 mu.

Example II A solution of 5 g. of allopregnane-3p,17,21- triol-20-one2l-monoacetate (Reichstein substance P esterified with acetic acid inthe 21- position) in 1 liter of tertiary butyl alcohol and 10 cc. ofpyridine was allowed to stand with 3.6 g. of N-bromoacetamide for 16hours. The reaction product allopregnane-fla, 21-diol-3,20- dione21-monoacetate crystallized from the solution and was filtered off.Thereafter it was recrystallized from ethyl alcohol and had a meltingpoint of 245-247 C. This compound was then treated in accordance withthe procedure of Example I and the resultant compound was A-pregnadien-1'7a, 21-diol-3,20-dione 21-acetate with a melting point of2l'7219 [a]D +83.0 (chloroform).

Eacample III 10 g. of the allopregnane-17,21-diol-3,20-dione21-monoacetate, prepared in accordance with Example II, were dissolvedin 3 liters of glacial acetic acid and 3 drops of hydrobromic acid and4.1 g. of bromine dissolved in 48 cc. of glacial acetic acid were thenadded. After standing for ten minutes the solution was then poured intowater and the precipitate filtered off and washed with water. The driedproduct was recrystallized from methyl alcohol. 2-bromoa1lopregnane-17a-2l-diol-3,2 0-dione 21-monoacetate was produced which melted at 290-201C. (with decomposition).

A solution of 1.4 g. of 2-bromoallopregnanel7a-21-diol-3,20-dione21-monoacetate was prepared in 200 cc. of glacial acetic acid and 2drops of hydrogen bromide. To the solution was added 5.8 cc. of asolution of bromine (83 mg./cc.) in acetic acid. After standing eighteenhours at room temperature the product was precipitated by the additionof water and recrystallized from hexane-acetone. The resultant2,4-dibromo compound had a melting point of 172-1'76 C. (withdecomposition) [a] +31.0 (chloroform). 1.3 g. of the dibromoketone weredehydrobrominated by boiling for one hour with 8 cc. of collidine andthe resultant mixture was worked up according to the procedure ofExample I. The product A -pregnadien-17a,21-diol-3,20-dione Zl-acetatehad a melting point of 217-219 C. [a] +88.0 (chloroform) It will beobvious to those skilled in the art that various changes may be madewithout departing from the spirit of the invention and 4 therefore theinvention is not' limited to what is described in the specification butonly as indicated in the appended claims.

We claim:

1. A new compound consisting of a A dien-3- one of theI'M-hydroxypregnane series.

2. A new compound consisting of A -pregnadien-17a-ol-3,20-di0ne with amelting point of 232-234 C.

3. A new compound consisting of A -pregnadien-17a,21-dio1-3,20-dione21-acetate with a melting point of 2l7-219 C.

CARL DJERASSI. GEORGE ROSENKRANZ. JUAN BERLIN.

No references cited.

1. A NEW COMPOUND CONSISTING OF A $1,4-DIEN-3ONE OF THE17A-HYDROXYPREGNANE SERIES.